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Soldier Repatriation
Soldier repatriation from Afghanistan has impacted debate about the war. This study highlights this impact with particular focus on Britain, Denmark and Germany. All three countries deployed soldiers soon after the 9/11 attacks, yet their role in Afghanistan and the casualty rates suffered, have been vastly different. This book looks at how their casualties influenced the framing of the war by analysing the political discourse about the casualties, how the media covered the repatriation and the burials, and how the dead were officially recognised and commemorated. Explaining how bodies count is not done exclusively by focusing on the political leadership and the media in the three countries, the response from the men and women in Afghanistan to the official framing of the war is given particular weight. Martinsen contributes to our understanding of European strategic culture by showing how countries respond to the same security challenges.
eBook
Archaeology of the Books of Samuel
Considering the literary dimension of the earliest text history of Samuel, this volume asks the question if the comparative analysis of the textual witnesses permit proving the existence of distinct literary editions and identifying the ideological motives that governed the possible modification of the text.
eBook
Structural and functional insights into 5′-ppp RNA pattern recognition by the innate immune receptor RIG-I
RIG-I is a cytosolic helicase that senses 5'-ppp RNA contained in negative-strand RNA viruses and triggers innate antiviral immune responses. Calorimetric binding studies established that the RIG-I C-terminal regulatory domain (CTD) binds to blunt-end double-stranded 5'-ppp RNA a factor of 17 more tightly than to its single-stranded counterpart. Here we report on the crystal structure of RIG-I CTD bound to both blunt ends of a self-complementary 5'-ppp dsRNA 12-mer, with interactions involving 5'-pp clearly visible in the complex. The structure, supported by mutation studies, defines how a lysine-rich basic cleft within the RIG-I CTD sequesters the observable 5'-pp of the bound RNA, with a stacked phenylalanine capping the terminal base pair. Key intermolecular interactions observed in the crystalline state are retained in the complex of 5'-ppp dsRNA 24-mer and full-length RIG-I under in vivo conditions, as evaluated from the impact of binding pocket RIG-I mutations and 2'-OCH(3) RNA modifications on the interferon response.
Journal Article
The phantom image : seeing the dead in ancient Rome
How could something as insubstantial as a ghost be made visible through the material grit of stone and paint? In this original and wide-ranging study, Patrick R. Crowley uses the figure of the ghost to offer a new understanding of the status of the image in Roman art and visual culture. Tracing the shifting practices and debates in antiquity about the nature of vision and representation, Crowley shows how images of ghosts make visible structures of beholding and strategies of depiction. Yet the figure of the ghost simultaneously contributes to a broader conceptual history that accounts for how modalities of belief emerged and developed in antiquity. Neither illustrations of ancient beliefs in ghosts nor depictions of the afterlife more generally, these images ultimately show us something about the visual event of seeing itself. The Phantom Image will be essential for anyone interested in ancient art, visual culture, and the history of the image.
Book
Caenorhabditis elegans Dicer acts with the RIG-I-like helicase DRH-1 and RDE-4 to cleave dsRNA
Invertebrates use the endoribonuclease Dicer to cleave viral dsRNA during antiviral defense, while vertebrates use RIG-I-like Receptors (RLRs), which bind viral dsRNA to trigger an interferon response. While some invertebrate Dicers act alone during antiviral defense,
Dicer acts in a complex with a dsRNA binding protein called RDE-4, and an RLR ortholog called DRH-1. We used biochemical and structural techniques to provide mechanistic insight into how these proteins function together. We found RDE-4 is important for ATP-independent and ATP-dependent cleavage reactions, while helicase domains of both DCR-1 and DRH-1 contribute to ATP-dependent cleavage. DRH-1 plays the dominant role in ATP hydrolysis, and like mammalian RLRs, has an N-terminal domain that functions in autoinhibition. A cryo-EM structure indicates DRH-1 interacts with DCR-1's helicase domain, suggesting this interaction relieves autoinhibition. Our study unravels the mechanistic basis of the collaboration between two helicases from typically distinct innate immune defense pathways.
Journal Article
Structure of the human DICER-pre-miRNA complex in a dicing state
Dicer has a key role in small RNA biogenesis, processing double-stranded RNAs (dsRNAs)
. Human DICER (hDICER, also known as DICER1) is specialized for cleaving small hairpin structures such as precursor microRNAs (pre-miRNAs) and has limited activity towards long dsRNAs-unlike its homologues in lower eukaryotes and plants, which cleave long dsRNAs. Although the mechanism by which long dsRNAs are cleaved has been well documented, our understanding of pre-miRNA processing is incomplete because structures of hDICER in a catalytic state are lacking. Here we report the cryo-electron microscopy structure of hDICER bound to pre-miRNA in a dicing state and uncover the structural basis of pre-miRNA processing. hDICER undergoes large conformational changes to attain the active state. The helicase domain becomes flexible, which allows the binding of pre-miRNA to the catalytic valley. The double-stranded RNA-binding domain relocates and anchors pre-miRNA in a specific position through both sequence-independent and sequence-specific recognition of the newly identified 'GYM motif'
. The DICER-specific PAZ helix is also reoriented to accommodate the RNA. Furthermore, our structure identifies a configuration of the 5' end of pre-miRNA inserted into a basic pocket. In this pocket, a group of arginine residues recognize the 5' terminal base (disfavouring guanine) and terminal monophosphate; this explains the specificity of hDICER and how it determines the cleavage site. We identify cancer-associated mutations in the 5' pocket residues that impair miRNA biogenesis. Our study reveals how hDICER recognizes pre-miRNAs with stringent specificity and enables a mechanistic understanding of hDICER-related diseases.
Journal Article